Resveratrol -Induced Demethylation of LATS1 and LATS2 Genes in Oral Squamous Cell Carcinoma

Meenakshi Jha; Abhijit Debnath; Anju Shrivastava; Sushma Chauhan

doi:10.31557/APJCB.2026.11.4.1137

Authors

Meenakshi Jha Amity Institute of Biotechnology, Amity University, Raipur, Chhattisgarh, 493225, India. Department of Zoology, University of Delhi, Delhi, 110007, India.
Abhijit Debnath Department of Pharmaceutics, Noida Institute of Engineering and Technology (Pharmacy Institute), 19 Knowledge Park-II, Institutional Area, Greater Noida-201306, Uttar Pradesh, India.
Anju Shrivastava Department of Zoology, University of Delhi, Delhi, 110007, India.
Sushma Chauhan Amity Institute of Biotechnology, Amity University, Raipur, Chhattisgarh, 493225, India.

DOI:

https://doi.org/10.31557/APJCB.2026.11.4.1137

Keywords:

Promoter hypermethylation, Tumor Suppressor Genes (TSGs), Epigenetic modifications, Resveratrol, LATS1/2

Abstract

Objective: This study aimed to investigate the potential of Resveratrol in reversing promoter hypermethylation of LATS1/2 genes, key components of the Hippo Signaling Pathway, in OSCC cell lines.

Materials and Methods: In vitro investigation was conducted after getting encouraging outcomes from consensus molecular docking & molecular dynamics (MD) simulations upto 100 nanoseconds. In vitro studies were conducted using CAL33 and SCC84 OSCC cell lines. Cell viability of the cells was assessed by MTT assay method to determine IC50 values. Cellular morphological changes induced by treatment were observed under microscope in comparison to control cells. Migration ability of cells was examined by wound healing assay, whereas apoptotic induction was confirmed through DNA fragmentation analysis. and To assess methylation reversal, extracted DNA is subjected to sodium bisulfite treatment followed by methylation-specific PCR (MS-PCR).

Results: Resveratrol exhibited IC50 values of 130.14 μM and 133.94 μM in CAL33 and SCC84 cells respectively, induced apoptotic body formation, significantly inhibited cell migration, and caused DNA fragmentation, while crucially, MS-PCR analysis revealed progressive demethylation of LATS1/2 genes over six days at 25 μM concentration. This is shown by a reduction in methylation-specific bands intensity.

Conclusion: These findings demonstrate that resveratrol effectively reverses promoter hypermethylation of LATS1/2 genes in OSCC cells through DNMT inhibitory activity at subcytotoxic doses, representing a promising non-toxic epigenetic therapeutic agent for oral cancer treatment with potential for clinical translation.